文章基本信息

标题：Altered adrenal gland cholesterol metabolism in the apoE-deficient mouse
本地全文：下载
作者：Fayanne E. Thorngate ; Penelope A. Strockbine ; Sandra K. Erickson 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2002
卷号：43
期号：11
页码：1920-1926
DOI：10.1194/jlr.M200205-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Previous studies suggest the hypothesis that apoE produced by adrenocortical cells modulates cellular cholesterol metabolism to enhance the storage of esterified cholesterol (EC) at the expense of cholesterol delivery to the steroidogenic pathway. In the present study, parameters of adrenal cholesterol metabolism and corticosteroid production were examined in wild type and apoE-deficient ( apoe ^−/− ) mice. Adrenal gland EC content and the EC/free cholesterol (FC) ratio in mice stressed by adrenocorticotropin (ACTH) treatment or saline injection were reduced in apoe ⁻ ^/ ⁻ compared to apoe ⁺ ^/ ⁺ mice. Relative to apoe ⁺ ^/ ⁺ mice, apoE deficiency also resulted in increased levels of plasma corticosterone in the basal state, in response to acute or long-term ACTH treatment, and after a swim-induced neuroendocrine-directed stress test. Measurements of adrenal gland scavenger receptor class B, type I (SR-BI), LDL receptor, and LDL receptor related protein (LRP) levels and the activities of ACAT or HMG-CoA reductase showed no difference between genotypes. Apoe ⁻ ^/ ⁻ and apoe ⁺ ^/ ⁺ mice showed similar quantitative increases in LDL receptors, SR-BI, adrenal weight gain, and ACAT activities in response to ACTH, and both genotypes had similar basal plasma ACTH concentrations. These results suggest that the effects of apoE deficiency reflect events at the level of the adrenal gland and are specific to changes in cholesterol accumulation and corticosterone production. Further, these findings support the hypothesis that apoE acts to enhance adrenocortical EC accumulation and diminish corticosterone production.